New molecular mechanisms to explain the neuroprotective effects of insulin-like growth factor II in a cellular model of Parkinson's disease.

INTRODUCTION: One of the hallmarks of Parkinsons Disease (PD) is oxidative distress, leading to mitochondrial dysfunction and neurodegeneration. Insulin-like growth factor II (IGF-II) has been proven to have antioxidant and neuroprotective effects in some neurodegenerative diseases, including PD. Consequently, there isgrowing interest in understanding the different mechanisms involved in the neuroprotective effect of this hormone. OBJECTIVES: To clarify the mechanism of action of IGF-II involved in the protective effect of this hormone. METHODS: The present study was carried out on a cellular model PD based on the incubation of dopaminergic cells (SN4741) in a culture with the toxic 1-methyl-4-phenylpyridinium (MPP+), in the presence of IGF-II. This model undertakes proteomic analyses in order to understand which molecular cell pathways might be involved in the neuroprotective effect of IGF-II. The most important proteins found in the proteomic study were tested by Western blot, colorimetric enzymatic activity assay and immunocytochemistry. Along with the proteomic study, mitochondrial morphology and function were also studied by transmission electron microscopy and oxygen consumption rate. The cell cycle was also analysed using 7AAd/BrdU staining, and flow cytometry. RESULTS: The results obtained indicate that MPP+, MPP++IGF-II treatment and IGF-II, when compared to control, modified the expression of 197, 246 proteins and 207 respectively. Some of these proteins were found to be involved in mitochondrial structure and function, and cell cycle regulation. Including IGF-II in the incubation medium prevents the cell damage induced by MPP+, recovering mitochondrial function and cell cycle dysregulation, and thereby decreasing apoptosis. CONCLUSION: IGF-II improves mitochondrial dynamics by promoting the association of Mitofilin with mitochondria, regaining function and redox homeostasis. It also rebalances the cell cycle, reducing the amount of apoptosis and cell death by the regulation of transcription factors, such as Checkpoint kinase 1.

Relevancia clínica de la técnica de utilización de inhaladores en pacientes con enfermedad pulmonar obstructiva crónica / The clinical relevance of inhalation technique in chronic obstructive pulmonary disease patients

Introducción:Numerosos estudios muestran que los pacientes con Enfermedad Pulmonar Obstructiva Crónica (EPOC) realizan una técnica de inhalación (TI) incorrecta. Nuestra investigación pretende describir los errores cometidos y la Importancia Clínica de dichos Fallos (ICF), e identificar los factores relacionados con ello.Pacientes y métodos:Estudio descriptivo transversal de 995 pacientes seguidos en 20 Centros de Salud de Andalucía. Se recogieron variables sociodemográficas, calidad de vida, estado mental-cognitivo, espirometría, gravedad, número de dispositivos, realización correcta de la TI, instrucción previa e ICF.Resultados:906 pacientes (91,1%) realizaban una TI incorrecta. Los errores más frecuentes presentaban ICF2-moderada y se relacionaron con nivel cognitivo bajo, pico flujo inhalatorio bajo y menos visitas al neumólogo. Los errores críticos-ICF3 mostraron relación con mayor gravedad, uso de Turbuhaler® y peor calidad de vida.Discusión:Altísima tasa de técnica incorrecta cuyos errores más frecuentes comprometen de forma moderada la eficacia del fármaco, se relacionan con el modo de realizar la TI y no con la dificultad en el manejo del dispositivo. Esto muestra la importancia de entrenar correctamente a nuestros pacientes. (AU)

Introduction:Numerous studies show that patients with chronic obstructive pulmonary disease (COPD) perform an incorrect inhalation technique (IT). This research aims to describe inhalation errors committed and their clinical importance, and to identify factors related to them.Patients and methods:A total of 995 patients were recruited in this cross-sectional, descriptive study that was conducted across 20 Andalusian Health Care Centres. The following variables were collected: socio-demographic data, quality of life, mental and cognitive status, spirometry tests, severity, number of IT devices, IT correct performance, previous instruction and clinical importance of errors.Results:Of the 995 patients, 906 (91,1%) performed an incorrect IT. The most common errors showed moderate errors, which were related to low-cognitive level, low-peak expiratory flow and fewer medical consultations with the pulmonologist. Critical errors were correlated with greater severity, usage of Turbuhaler® and worse quality of life.Discussion:Soaring incorrect technique rate, whose most common errors sparingly compromise the drug effectiveness. These errors are related to the way the patients perform the IT, and not to the difficulty in handling the device. This information demonstrates the relevance of training patients in a proper way. (AU)

Mejora de la función pulmonar en fibrosis quística mediante insuflación-exuflación mecánica / Improved lung function in cystic fibrosis using mechanical insufflation-exsufflation

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Caracterización de receptores muscarínicos en células indiferenciadas tiroideas de ratas Fisher / Characterization of undifferentiated muscarinic thyroid cells in fisher rats

Introducción: El sistema nervioso autónomo parasimpático tiene el control de la función tiroidea mediante la activación de receptores muscarínicos en las células foliculares. Se han identificado diversos subtipos farmacológicos y moleculares de receptores muscarínicos (M1, M2, M3, M4, M5) tanto en el sistema nervioso central (SNC) como en los tejidos periféricos, pero hay controversia acerca de su caracterización en las células tiroideas. Material y métodos: Cultivos celulares de células epiteliales tiroideas indiferenciadas de ratas Fisher (FRT). Estudios de unión de receptores a radioligando: cinéticas de asociación, cinéticas de disociación y competiciones entre diversos fármacos antagonistas selectivos muscarínicos; se utiliza, como radioligando, 3H-N-metil-escopolamina (3H-NMS). Resultados: Se observa que hay receptores específicos muscarínicos en la membrana plasmática de las células FRT con una constante de disociación en equilibrio (Kd) de 0,44 nmol. El orden de afinidades de los diferentes antagonistas muscarínicos encontrado en membranas epiteliales de células FRT mediante el ajuste de los datos para un modelo de un solo sitio de unión fue: diciclomina > hexahidrosiladifenidol (HHSD) = 4-difenilacetoxi-N-metilpiperidina metiodida (4-DAMP) > pirenzepina > himbacina = 11-[[2-[(dietil-amino)metil]-1-piperidinil]acetil]-5,11-dihidro-6H-pirido(414)benzodiacepina (AF-DX 116).Conclusiones: Los resultados obtenidos en este estudio indican que hay sitios de unión para 3H-NMS que se corresponden con los receptores muscarínicos localizados en células FRT. Los resultados obtenidos en los experimentos de competición indican que el receptor presente en esta localización se corresponde con el subtipo M3 (AU)

Introduction: The parasympathetic autonomous nervous system exerts control over thyroid function by activation of the muscarinic receptors in follicular cells. Various pharmacological and molecular subtypes of muscarinic receptors (M1, M2, M3, M4, M5) have been identified in central nervous system and peripheral tissues. Controversy surrounds receptor characterization in thyroid cells. Materials and methods: Undifferentiated Fisher rat thyroid epithelial cells (FRT) were cultured. Association and dissociation kinetics assays and antagonist competition studies of the binding of 3H-N-methylscopolamine (3H-NMS) to muscarinic receptors were performed to demonstrate the presence of muscarinic receptors. Results: Specific muscarinic receptors in the plasma membrane of FRT cells were observed with an equilibrium dissociation constant (Kd) of 0.44 nmol. The order of affinities obtained fitting the data to one binding site model in competition experiments with the muscarinic receptor antagonist was: dicyclomine > hexahydrosiladifenidol (HHSD) = 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) > pirenzepine > himbacine = 11-[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H-pyrido(414)benzodiazepine (AF-DX 116). Conclusions: The results obtained indicate the existence of specific 3H-NMS muscarinic binding sites located in the plasma membrane of FRT cells. The results obtained in competition experiments suggest that the receptors present in FRT cells belong to the M3 subtype (AU)